TY - JOUR
T1 - Consolidation and Maintenance in Newly Diagnosed Multiple Myeloma
AU - Sonneveld, Pieter
AU - Dimopoulos, Meletios A
AU - Beksac, Meral
AU - van der Holt, Bronno
AU - Aquino, Sara
AU - Ludwig, Heinz
AU - Zweegman, Sonja
AU - Zander, Thilo
AU - Zamagni, Elena
AU - Wester, Ruth
AU - Hajek, Roman
AU - Pantani, Lucia
AU - Dozza, Luca
AU - Gay, Francesca
AU - Cafro, AnneMaria
AU - De Rosa, Luca
AU - Morelli, Annamaria
AU - Gregersen, Henrik
AU - Gulbrandsen, Nina
AU - Cornelisse, Petra
AU - Troia, Rosella
AU - Oliva, Stefania
AU - van de Velden, Vincent
AU - Wu, KaLung
AU - Ypma, Paula F
AU - Bos, Gerard
AU - Levin, Mark-David
AU - Pour, Luca
AU - Driessen, Christoph
AU - Broijl, Annemiek
AU - Croockewit, Alexandra
AU - Minnema, Monique C
AU - Waage, Anders
AU - Hveding, Cecilie
AU - van de Donk, Niels W C J
AU - Offidani, Massimo
AU - Palumbo, Giuseppe A
AU - Spencer, Andrew
AU - Boccadoro, Mario
AU - Cavo, Michele
N1 - Publisher Copyright:
© 2021 by American Society of Clinical Oncology.
PY - 2021/11/10
Y1 - 2021/11/10
N2 - PURPOSE To address the role of consolidation treatment for newly diagnosed, transplant eligible patients with multiple myeloma in a controlled clinical trial. PATIENTS AND METHODS The EMN02/HOVON95 trial compared consolidation treatment with two cycles of bortezomib, lenalidomide, and dexamethasone (VRD) or no consolidation after induction and intensification therapy, followed by continuous lenalidomide maintenance. Primary study end point was progression-free survival (PFS). RESULTS Eight hundred seventy-eight eligible patients were randomly assigned to receive VRD consolidation (451 patients) or no consolidation (427 patients). At a median follow-up of 74.8 months, median PFS with adjustment for pretreatment was prolonged in patients randomly assigned to VRD consolidation (59.3 v 42.9 months, hazard ratio [HR] 5 0.81; 95% CI, 0.68 to 0.96; P = .016). The PFS benefit was observed across most predefined subgroups, including revised International Staging System (ISS) stage, cytogenetics, and prior treatment. Revised ISS3 stage (HR, 2.00; 95% CI, 1.41 to 2.86) and ampl1q (HR, 1.67; 95% CI, 1.37 to 2.04) were significant adverse prognostic factors. The median duration of maintenance was 33 months (interquartile range 13-86 months). Response $ complete response (CR) after consolidation versus no consolidation before start of maintenance was 34% versus 18%, respectively (P <.001). Response $ CR on protocol including maintenance was 59% with consolidation and 46% without (P <.001). Minimal residual disease analysis by flow cytometry in a subgroup of 226 patients with CR or stringent complete response or very good partial response before start of maintenance demonstrated a 74% minimal residual disease-negativity rate in VRDtreated patients. Toxicity from VRD was acceptable and manageable. CONCLUSION Consolidation treatment with VRD followed by lenalidomide maintenance improves PFS and depth of response in newly diagnosed patients with multiple myeloma as compared to maintenance alone.
AB - PURPOSE To address the role of consolidation treatment for newly diagnosed, transplant eligible patients with multiple myeloma in a controlled clinical trial. PATIENTS AND METHODS The EMN02/HOVON95 trial compared consolidation treatment with two cycles of bortezomib, lenalidomide, and dexamethasone (VRD) or no consolidation after induction and intensification therapy, followed by continuous lenalidomide maintenance. Primary study end point was progression-free survival (PFS). RESULTS Eight hundred seventy-eight eligible patients were randomly assigned to receive VRD consolidation (451 patients) or no consolidation (427 patients). At a median follow-up of 74.8 months, median PFS with adjustment for pretreatment was prolonged in patients randomly assigned to VRD consolidation (59.3 v 42.9 months, hazard ratio [HR] 5 0.81; 95% CI, 0.68 to 0.96; P = .016). The PFS benefit was observed across most predefined subgroups, including revised International Staging System (ISS) stage, cytogenetics, and prior treatment. Revised ISS3 stage (HR, 2.00; 95% CI, 1.41 to 2.86) and ampl1q (HR, 1.67; 95% CI, 1.37 to 2.04) were significant adverse prognostic factors. The median duration of maintenance was 33 months (interquartile range 13-86 months). Response $ complete response (CR) after consolidation versus no consolidation before start of maintenance was 34% versus 18%, respectively (P <.001). Response $ CR on protocol including maintenance was 59% with consolidation and 46% without (P <.001). Minimal residual disease analysis by flow cytometry in a subgroup of 226 patients with CR or stringent complete response or very good partial response before start of maintenance demonstrated a 74% minimal residual disease-negativity rate in VRDtreated patients. Toxicity from VRD was acceptable and manageable. CONCLUSION Consolidation treatment with VRD followed by lenalidomide maintenance improves PFS and depth of response in newly diagnosed patients with multiple myeloma as compared to maintenance alone.
UR - http://www.scopus.com/inward/record.url?scp=85121950254&partnerID=8YFLogxK
U2 - 10.1200/JCO.21.01045
DO - 10.1200/JCO.21.01045
M3 - Article
C2 - 34520219
SN - 0732-183X
VL - 39
SP - 3613
EP - 3622
JO - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
IS - 32
ER -